Gene therapy for the peripheral nervous system: a strategy to repair the injured nerve?

Peripheral nerve injury in humans often leads to incomplete functional recovery. In this review we discuss the potential for gene therapy to be used as a strategy alongside surgical repair techniques for the study of peripheral nerve regeneration in rodent models and with a view to its eventual use for the promotion of successful regeneration in the clinic. Gene therapy vectors based on herpes simplex virus, adenovirus, lentivirus and adeno-associated virus have been developed to deliver genes to the neurons of the peripheral nervous system, i.e. primary sensory neurons in the dorsal root ganglia and primary motor neurons. Adenoviral and lentiviral vectors have also been used to transduce Schwann cells and fibroblasts in the injured nerve. We present an overview of these vectors, their application so far in the peripheral nervous system, their potential as vectors for enhancing peripheral nerve repair, and the successful interventions that have been demonstrated in animal models. We also discuss some of the limitations of current vectors and how they may be overcome. While the technology for gene delivery is approaching a state of readiness for clinical translation, the current range of therapeutic genes for the repair of the traumatically injured peripheral nerve is mostly limited to neurotrophic factors delivered to neurons, Schwann cells or possibly the target organs. Finally, therefore, we consider what type of therapeutic transgene may be desirable to enhance nerve regeneration in the future.